tbuckley/cabot-search huggingface dataset:
Open-Label, Randomized, Multicenter, Phase III Study Comparing Oral Paclitaxel Plus Encequidar Versus Intravenous Paclitaxel in Patients With Metastatic Breast Cancer
Authors: Hope S. Rugo, Gerardo A. Umanzor, Francisco J. Barrios, Rosa H. Vasallo, Marco A. Chivalan, Suyapa Bejarano, Julio R. Ramírez, Luis Fein, Ruben D. Kowalyszyn, E. Douglas Kramer, Hui Wang, Min-Fun R. Kwan, David L. Cutler
Journal: Journal of Clinical Oncology (2022)

Intravenous paclitaxel (IVpac) is complicated by neuropathy and requires premedication to prevent hypersensitivity-type reactions. Paclitaxel is poorly absorbed orally; encequidar (E), a novel P-glycoprotein pump inhibitor, allows oral absorption.A phase III open-label study comparing oral paclitaxel plus E (oPac + E) 205 mg/m2 paclitaxel plus 15 mg E methanesulfonate monohydrate 3 consecutive days per week versus IVpac 175 mg/m2 once every 3 weeks was performed. Women with metastatic breast cancer and adequate organ function, at least 1 year from last taxane, were randomly assigned 2:1 to oPac + E versus IVpac. The primary end point was confirmed radiographic response using RECIST 1.1, assessed by blinded independent central review. Secondary end points included progression-free survival (PFS) and overall survival (OS).Four hundred two patients from Latin America were enrolled (265 oPac + E, 137 IVpac); demographics and prior therapies were balanced. The confirmed response (intent-to-treat) was 36% for oPac + E versus 23% for IVpac (P = .01). The PFS was 8.4 versus 7.4 months, respectively (hazard ratio, 0.768; 95.5% CI, 0.584 to 1.01; P = .046), and the OS was 22.7 versus 16.5 months, respectively (hazard ratio, 0.794; 95.5% CI, 0.607 to 1.037; P = .08). Grade 3-4 adverse reactions were 55% with oPac + E and 53% with IVpac. oPac + E had lower incidence and severity of neuropathy (2% v 15% > grade 2) and alopecia (49% v 62% all grades) than IVpac but more nausea, vomiting, diarrhea, and neutropenic complications, particularly in patients with elevated liver enzymes. On-study deaths (8% oPac + E v 9% IVpac) were treatment-related in 3% and 0%, respectively.oPac + E increased the confirmed tumor response versus IVpac, with trends in PFS and OS. Neuropathy was less frequent and severe with oPac + E; neutropenic serious infections were increased. Elevated liver enzymes at baseline predispose oPac + E patients to early neutropenia and serious infections (funded by Athenex, Inc; ClinicalTrials.gov identifier: NCT02594371).
Improving the diagnosis of severe malaria in African children using platelet counts and plasma <i>Pf</i> HRP2 concentrations
Authors: James A. Watson, Sophie Uyoga, Perpetual Wanjiku, Johnstone Makale, Gideon M. Nyutu, Neema Mturi, Elizabeth C. George, Charles J. Woodrow, Nicholas P. J. Day, Philip Bejon, Robert O. Opoka, Arjen M. Dondorp, Chandy C. John, Kathryn Maitland, Thomas N. Williams, Nicholas J. White
Journal: Science Translational Medicine (2022)

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Effectiveness of Intensive Versus Minimalist Follow-Up Regimen on Survival in Patients With Endometrial Cancer (TOTEM Study): A Randomized, Pragmatic, Parallel Group, Multicenter Trial
Authors: Paolo Zola, Giovannino Ciccone, Elisa Piovano, Luca Fuso, Daniela Di Cuonzo, Anna Castiglione, Eva Pagano, Elena Peirano, Fabio Landoni, Enrico Sartori, Fabrice Narducci, Oscar Bertetto, Annamaria Ferrero
Journal: Journal of Clinical Oncology (2022)

In the absence of clear evidence from randomized trials, the intensity of follow-up regimens after surgical treatment of endometrial cancer is highly variable in clinical practice. To reduce this uncertainty, we conducted a randomized trial to test whether an intensive (INT) versus a minimalist (MIN) follow-up regimen improves overall survival (OS) in patients undergoing operation for endometrial cancer.The TOTEM study was a large, pragmatic randomized trial, conducted in 42 hospitals (in Italy and France) including patients surgically treated for endometrial cancer, in complete clinical remission, International Federation of Gynecology and Obstetrics stage I-IV. After stratification by center and risk of relapse (low or high), patients were randomly assigned (1:1) to INT or MIN hospital-based follow-up regimens. The study was powered to demonstrate an absolute improvement of 5% of the 5-year OS with the INT regimen.In total, 1,871 patients were randomly assigned between November 2008 and July 2018, and 1,847 patients (98.7%) were available for the final analysis (60% low risk). After a median follow-up of 69 months, the 5-year OS was 90.6% in the INT and 91.9% in the MIN arms (hazard ratio, 1.13, 95% CI, 0.86 to 1.50, P = .380). No differences in OS were found in subgroup analyses considering age, cancer treatment, risk of relapse, and degree of adherence of the center to the scheduled follow-up. The probability of detecting a relapse was slightly higher in the INT arm (hazard ratio, 1.17; 95% CI, 0.92 to 1.48; P = .194).An INT follow-up in endometrial cancer-treated patients does not improve OS, even in high-risk patients. According to available evidence, there is no need to routinely add vaginal cytology, laboratory, or imaging investigations to the MIN regimens used in this trial.
Interleukin-6–dependent epithelial fluidization initiates fibrotic lung remodeling
Authors: Ian T. Stancil, Jacob E. Michalski, Corinne E. Hennessy, Kristina L. Hatakka, Ivana V. Yang, Jonathan S. Kurche, Mercedes Rincon, David A. Schwartz
Journal: Science Translational Medicine (2022)

Chronic disease results from the failure of tissues to maintain homeostasis. In the lung, coordinated repair of the epithelium is essential for preserving homeostasis. In animal models and human lung disease, airway epithelial cells mobilize in response to lung injury, resulting in the formation of airway-like cysts with persistent loss of functional cell types and parenchymal architecture. Using live-cell imaging of human lung epithelial cultures and mouse precision-cut lung slices, we demonstrated that distal airway epithelia are aberrantly fluidized both after injury and in fibrotic lung disease. Through transcriptomic profiling and pharmacologic stimulation of epithelial cultures, we identified interleukin-6 (IL-6) signaling as a driver of tissue fluidization. This signaling cascade occurred independently of canonical Janus kinase (JAK)–signal transducer and activator of transcription (STAT) signaling but instead was dependent on a downstream SRC family kinase (SFK)–yes-associated protein (YAP) axis. Airway epithelial-fibroblast cocultures revealed that the fibrotic mesenchyme acts as a source of IL-6 family cytokines, which drive airway fluidization. Inhibition of the IL-6–SFK–YAP cascade was sufficient to prevent fluidization in both in vitro and ex vivo models. Last, we demonstrated a reduction in fibrotic lung remodeling in mice through genetic or pharmacologic targeting of IL-6–related signaling. Together, our findings illustrate the critical role of airway epithelial fluidization in coordinating the balance between homeostatic lung repair and fibrotic airspace remodeling.
Artificial Intelligence and Deep Learning for Rheumatologists
Authors: Christopher McMaster, Alix Bird, David F. L. Liew, Russell R. Buchanan, Claire E. Owen, Wendy W. Chapman, Douglas E. V. Pires
Journal: Arthritis & Rheumatology (2022)

Deep learning has emerged as the leading method in machine learning, spawning a rapidly growing field of academic research and commercial applications across medicine. Deep learning could have particular relevance to rheumatology if correctly utilized. The greatest benefits of deep learning methods are seen with unstructured data frequently found in rheumatology, such as images and text, where traditional machine learning methods have struggled to unlock the trove of information held within these data formats. The basis for this success comes from the ability of deep learning to learn the structure of the underlying data. It is no surprise that the first areas of medicine that have started to experience impact from deep learning heavily rely on interpreting visual data, such as triaging radiology workflows and computer-assisted colonoscopy. Applications in rheumatology are beginning to emerge, with recent successes in areas as diverse as detecting joint erosions on plain radiography, predicting future rheumatoid arthritis disease activity, and identifying halo sign on temporal artery ultrasound. Given the important role deep learning methods are likely to play in the future of rheumatology, it is imperative that rheumatologists understand the methods and assumptions that underlie the deep learning algorithms in widespread use today, their limitations and the landscape of deep learning research that will inform algorithm development, and clinical decision support tools of the future. The best applications of deep learning in rheumatology must be informed by the clinical experience of rheumatologists, so that algorithms can be developed to tackle the most relevant clinical problems.
Rare Case of Isolated Systemic Arterial Supply to Upper Lobe of Left Lung
Authors: Navjot Kaur, Swathi Raman, Vruksha Upadhyay, Maruti Kumaran, Parth Rali, Massa Zantah
Journal: American Journal of Respiratory and Critical Care Medicine (2022)

"Rare Case of Isolated Systemic Arterial Supply to Upper Lobe of Left Lung." American Journal of Respiratory and Critical Care Medicine, 206(9), pp. 1163–1165
Intranasal vaccination with lipid-conjugated immunogens promotes antigen transmucosal uptake to drive mucosal and systemic immunity
Authors: Brittany L. Hartwell, Mariane B. Melo, Peng Xiao, Ashley A. Lemnios, Na Li, Jason Y.H. Chang, Jingyou Yu, Makda S. Gebre, Aiquan Chang, Laura Maiorino, Crystal Carter, Tyson J. Moyer, Neil C. Dalvie, Sergio A. Rodriguez-Aponte, Kristen A. Rodrigues, Murillo Silva, Heikyung Suh, Josetta Adams, Jane Fontenot, J. Christopher Love, Dan H. Barouch, Francois Villinger, Ruth M. Ruprecht, Darrell J. Irvine
Journal: Science Translational Medicine (2022)

To combat the HIV epidemic and emerging threats such as SARS-CoV-2, immunization strategies are needed that elicit protection at mucosal portals of pathogen entry. Immunization directly through airway surfaces is effective in driving mucosal immunity, but poor vaccine uptake across the mucus and epithelial lining is a limitation. The major blood protein albumin is constitutively transcytosed bidirectionally across the airway epithelium through interactions with neonatal Fc receptors (FcRn). Exploiting this biology, here, we demonstrate a strategy of “albumin hitchhiking” to promote mucosal immunity using an intranasal vaccine consisting of protein immunogens modified with an amphiphilic albumin-binding polymer-lipid tail, forming amph-proteins. Amph-proteins persisted in the nasal mucosa of mice and nonhuman primates and exhibited increased uptake into the tissue in an FcRn-dependent manner, leading to enhanced germinal center responses in nasal-associated lymphoid tissue. Intranasal immunization with amph-conjugated HIV Env gp120 or SARS-CoV-2 receptor binding domain (RBD) proteins elicited 100- to 1000-fold higher antigen-specific IgG and IgA titers in the serum, upper and lower respiratory mucosa, and distal genitourinary mucosae of mice compared to unmodified protein. Amph-RBD immunization induced high titers of SARS-CoV-2–neutralizing antibodies in serum, nasal washes, and bronchoalveolar lavage. Furthermore, intranasal amph-protein immunization in rhesus macaques elicited 10-fold higher antigen-specific IgG and IgA responses in the serum and nasal mucosa compared to unmodified protein, supporting the translational potential of this approach. These results suggest that using amph-protein vaccines to deliver antigen across mucosal epithelia is a promising strategy to promote mucosal immunity against HIV, SARS-CoV-2, and other infectious diseases.
Dendrimer nanotherapy for severe COVID-19 attenuates inflammation and neurological injury markers and improves outcomes in a phase2a clinical trial
Authors: Aaron M. Gusdon, Nauder Faraday, John S. Aita, Sunil Kumar, Ishan Mehta, HuiMahn A. Choi, Jeffery L. Cleland, Keith Robinson, Louise D. McCullough, Derek K. Ng, Rangaramanujam M. Kannan, Sujatha Kannan
Journal: Science Translational Medicine (2022)

Hyperinflammation triggered by SARS-CoV-2 is a major cause of disease severity, with activated macrophages implicated in this response. OP-101, a hydroxyl-polyamidoamine dendrimer– N -acetylcysteine conjugate that specifically targets activated macrophages, improves outcomes in preclinical models of systemic inflammation and neuroinflammation. In this multicenter, randomized, double-blind, placebo-controlled, adaptive phase 2a trial, we evaluated safety and preliminary efficacy of OP-101 in patients with severe COVID-19. Twenty-four patients classified as having severe COVID-19 with a baseline World Health Organization seven-point ordinal scale of ≥5 were randomized to receive a single intravenous dose of placebo ( n = 7 patients) or OP-101 at 2 ( n = 6), 4 ( n = 6), or 8 mg/kg ( n = 5 patients). All study participants received standard of care, including corticosteroids. OP-101 at 4 mg/kg was better than placebo at decreasing inflammatory markers; OP-101 at 4 and 8 mg/kg was better than placebo at reducing neurological injury markers, (neurofilament light chain and glial fibrillary acidic protein). Risk for the composite outcome of mechanical ventilation or death at 30 and 60 days after treatment was 71% (95% CI: 29%, 96%) for placebo and 18% (95% CI: 4%, 43%; P = 0.021) for the pooled OP-101 treatment arms. At 60 days, 3 of 7 patients given placebo and 14 of 17 OP-101–treated patients were surviving. No drug-related adverse events were reported. These data show that OP-101 was well tolerated and may have potential to treat systemic inflammation and neuronal injury, reducing morbidity and mortality in hospitalized patients with severe COVID-19.
A semaphorin-plexin-Rasal1 signaling pathway inhibits gastrin expression and protects against peptic ulcers
Authors: Rui Xu, Carsten Höß, Jakub M. Swiercz, Dominique T. Brandt, Veronika Lutz, Natalia Petersen, Rui Li, Dandan Zhao, Arkadiusz Oleksy, Tilbe Creigh-Pulatmen, Martina Trokter, Marina Fedorova, Ann Atzberger, Rune B. Strandby, August A. Olsen, Michael P. Achiam, David Matthews, Magdalena Huber, Hermann-Josef Gröne, Stefan Offermanns, Thomas Worzfeld
Journal: Science Translational Medicine (2022)

Peptic ulcer disease is a frequent clinical problem with potentially serious complications such as bleeding or perforation. A decisive factor in the pathogenesis of peptic ulcers is gastric acid, the secretion of which is controlled by the hormone gastrin released from gastric G cells. However, the molecular mechanisms regulating gastrin plasma concentrations are poorly understood. Here, we identified a semaphorin-plexin signaling pathway that operates in gastric G cells to inhibit gastrin expression on a transcriptional level, thereby limiting food-stimulated gastrin release and gastric acid secretion. Using a systematic siRNA screening approach combined with biochemical, cell biology, and in vivo mouse experiments, we found that the RasGAP protein Rasal1 is a central mediator of plexin signal transduction, which suppresses gastrin expression through inactivation of the small GTPase R-Ras. Moreover, we show that Rasal1 is pathophysiologically relevant for the pathogenesis of peptic ulcers induced by nonsteroidal anti-inflammatory drugs (NSAIDs), a main risk factor of peptic ulcers in humans. Last, we show that application of recombinant semaphorin 4D alleviates peptic ulcer disease in mice in vivo, demonstrating that this signaling pathway can be harnessed pharmacologically. This study unravels a mode of G cell regulation that is functionally important in gastric homeostasis and disease.
Safety of motorized spiral enteroscopy: is what we know today enough?
Authors: Marco Pennazio
Journal: Endoscopy (2022)

Over the last 20 years, we have seen a fantastic evolution in small-bowel endoscopy, first with small-bowel capsule endoscopy and subsequently with device-assisted enteroscopy (DAE), including double-balloon enteroscopy (DBE), single-balloon enteroscopy (SBE), and manual spiral enteroscopy. Motorized spiral enteroscopy (MSE) represents the latest innovative advancement in enteroscopy [1]. MSE appears to offer several advantages compared with conventional DAE, which include: shorter procedure times, an apparently fast learning curve [1] [2] [3], and high total enteroscopy rates [4]. Of note, the rate of total enteroscopy through only an antegrade approach can be as high as 31.1 % [2]. The diagnostic yield is comparable to DAE. However, as with all new technologies, to allow for its widespread application in clinical practice, the most recent must not be inferior to the methods already available and, most importantly, it must have a comparable, or even a more favorable, safety profile.
Protection Associated with Previous SARS-CoV-2 Infection in Nicaragua
Authors: Hannah E Maier, Angel Balmaseda, Saira Saborio, Sergio Ojeda, Carlos Barilla, Nery Sanchez, Roger Lopez, Miguel Plazaola, Cristhiam Cerpas, Harm van Bakel, John Kubale, Eva Harris, Guillermina Kuan, Aubree Gordon
Journal: New England Journal of Medicine (2022)
Intrapulmonary Bronchopulmonary Anastomoses in Severe COVID-19–related Acute Respiratory Failure
Authors: Jenna Bodmer, Alice Levin, Christian Westöö, Oscar van der Have, Niccolò Peruzzi, Karin Tran-Lundmark, Steven H. Abman, Csaba Galambos
Journal: American Journal of Respiratory and Critical Care Medicine (2022)
Chinese Expert Consensus on Immunotherapy for Hepatocellular Carcinoma (2021 Edition)
Authors: Yu Yang, Juxian Sun, Mengchao Wu, Wan Yee Lau, Shusen Zheng, Xue-Hao Wang, Xiaoping Chen, Jia Fan, Jiahong Dong, Jianqiang Cai, Minshan Chen, Yongjun Chen, Zhangjun Cheng, Chaoliu Dai, Jianzhen Shan, Cheng-You Du, Chihua Fang, Heping Hu, Zhili Ji, Weidong Jia, Gong Li, Jing Li, Jiangtao Li, Chang Liu, Fubao Liu, Yong Ma, Yilei Mao, Zuoxing Niu, Jie Shen, Jie Shi, Xuetao Shi, Wenjie Song, Hui-Chuan Sun, Guang Tan, Ran Tao, Xiaohu Wang, Tianfu Wen, Liqun Wu, Jinglin Xia, Bang-De Xiang, Maolin Yan, Mingang Ying, Ling Zhang, Xuewen Zhang, Zhao Chong Zeng, Yubao Zhang, Zhiwei Zhang, Jie Zhou, Cuncai Zhou, Jun Zhou, Ledu Zhou, Xinmin Zhou, Ji Zhu, Zhenyu Zhu, Qi Zhang, Qiu Li, Shuqun Cheng
Journal: Liver Cancer (2022)

&lt;b&gt;&lt;i&gt;Background:&lt;/i&gt;&lt;/b&gt; Hepatocellular carcinoma (HCC) is one of the most common malignancies in China. Most HCC patients are first diagnosed at an advanced stage, and systemic treatments are the mainstay of treatment. &lt;b&gt;&lt;i&gt;Summary:&lt;/i&gt;&lt;/b&gt; In recent years, immune checkpoint inhibitors have made a breakthrough in the systemic treatment of middle-advanced HCC, breaking the single therapeutic pattern of molecular-targeted agents. To better guide the clinical treatment for effective and safe use of immunotherapeutic drugs, the Chinese Association of Liver Cancer and Chinese Medical Doctor Association has gathered multidisciplinary experts and scholars in relevant fields to formulate the “Chinese Clinical Expert Consensus on Immunotherapy for Hepatocellular Carcinoma (2021)” based on current clinical studies and clinical medication experience for reference in China. &lt;b&gt;&lt;i&gt;Key Messages:&lt;/i&gt;&lt;/b&gt; The consensus contained 17 recommendations, including the preferred regimen for first- and second-line immunotherapy, evaluation and monitoring before/during/after treatment, management of complications, precautions for special patients, and potential population for immunotherapy.
Efficacy of Antibodies and Antiviral Drugs against Omicron BA.2.12.1, BA.4, and BA.5 Subvariants
Authors: Emi Takashita, Seiya Yamayoshi, Viviana Simon, Harm van Bakel, Emilia M Sordillo, Andrew Pekosz, Shuetsu Fukushi, Tadaki Suzuki, Ken Maeda, Peter Halfmann, Yuko Sakai-Tagawa, Mutsumi Ito, Shinji Watanabe, Masaki Imai, Hideki Hasegawa, Yoshihiro Kawaoka
Journal: New England Journal of Medicine (2022)
Effectiveness of BNT162b2 Vaccine against Omicron in Children 5 to 11 Years of Age
Authors: Sharon H.X. Tan, Alex R. Cook, Derrick Heng, Benjamin Ong, David C. Lye, Kelvin B. Tan
Journal: New England Journal of Medicine (2022)

Since it was first identified in early November 2021, the B.1.1.529 (omicron) variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread quickly and replaced the B.1.617.2 (delta) variant as the dominant variant in many countries. Data on the real-world effectiveness of vaccines against the omicron variant in children are lacking.In a study conducted from January 21, 2022, through April 8, 2022, when the omicron variant was spreading rapidly, we analyzed data on children in Singapore who were 5 to 11 years of age. We assessed the incidences of all reported SARS-CoV-2 infections (confirmed on polymerase-chain-reaction [PCR] assay, rapid antigen testing, or both), SARS-CoV-2 infections confirmed on PCR assay, and coronavirus disease 2019 (Covid-19)-related hospitalizations among unvaccinated, partially vaccinated (≥1 day after the first dose of vaccine and up to 6 days after the second dose), and fully vaccinated children (≥7 days after the second dose). Poisson regression was used to estimate vaccine effectiveness from the incidence rate ratio of outcomes.A total of 255,936 children were included in the analysis. Among unvaccinated children, the crude incidence rates of all reported SARS-CoV-2 infections, PCR-confirmed SARS-CoV-2 infections, and Covid-19-related hospitalizations were 3303.5, 473.8, and 30.0 per 1 million person-days, respectively. Among partially vaccinated children, vaccine effectiveness was 13.6% (95% confidence interval [CI], 11.7 to 15.5) against all SARS-CoV-2 infections, 24.3% (95% CI, 19.5 to 28.9) against PCR-confirmed SARS-CoV-2 infection, and 42.3% (95% CI, 24.9 to 55.7) against Covid-19-related hospitalization; in fully vaccinated children, vaccine effectiveness was 36.8% (95% CI, 35.3 to 38.2), 65.3% (95% CI, 62.0 to 68.3), and 82.7% (95% CI, 74.8 to 88.2), respectively.During a period when the omicron variant was predominant, BNT162b2 vaccination reduced the risks of SARS-CoV-2 infection and Covid-19-related hospitalization among children 5 to 11 years of age.
Recognition of Drivers’ Hard and Soft Braking Intentions Based on Hybrid Brain-Computer Interfaces
Authors: Jiawei Ju, Aberham Genetu Feleke, Longxi Luo, Xinan Fan
Journal: Cyborg and Bionic Systems (2022)

In this paper, we propose simultaneous and sequential hybrid brain-computer interfaces (hBCIs) that incorporate electroencephalography (EEG) and electromyography (EMG) signals to classify drivers' hard braking, soft braking, and normal driving intentions to better assist driving for the first time. The simultaneous hBCIs adopt a feature-level fusion strategy (hBCI-FL) and classifier-level fusion strategies (hBCIs-CL). The sequential hBCIs include the hBCI-SE1, where EEG signals are prioritized to detect hard braking, and hBCI-SE2, where EMG signals are prioritized to detect hard braking. Experimental results show that the proposed hBCI-SE1 with spectral features and the one-vs-rest classification strategy performs best with an average system accuracy of 96.37% among hBCIs. This work is valuable for developing human-centric intelligent assistant driving systems to improve driving safety and driving comfort and promote the application of BCIs.
Burden of SARS-CoV-2 infection in healthcare workers during second wave in England and impact of vaccines: prospective multicentre cohort study (SIREN) and mathematical model
Authors: Diane Pople, Edward J M Monk, Stephanie Evans, Sarah Foulkes, Jasmin Islam, Edgar Wellington, Ana Atti, Russell Hope, Julie Robotham, Susan Hopkins, Colin S Brown, Victoria J Hall
Journal: BMJ (2022)

To describe the incidence of, risk factors for, and impact of vaccines on primary SARS-CoV-2 infection during the second wave of the covid-19 pandemic in susceptible hospital healthcare workers in England.